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    PCSK9

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    For Research Use Only. Not For Clinical Use.


    Background

    This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants.
    PCSK9
    Protein class

    Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins

    Predicted location

    Intracellular, Secreted (different isoforms)

    Single cell type specificity

    Cell type enhanced (Hepatocytes, Alveolar cells type 2, Alveolar cells type 1, Gastric mucus-secreting cells)

    Immune cell specificity

    Not detected in immune cells

    Cell line specificity

    Cell line enhanced (A-431, CACO-2, HaCaT, HeLa, RPTEC TERT1)

    Interaction

    Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers. Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full-length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR. Interacts (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the interaction inhibits the degradation of LDLR (PubMed:18799458).

    Molecular function

    Hydrolase, Protease, Serine protease

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